Low Testosterone in Aging Men

Joggers near the Washington Monument, an obelisk at the National Mall in Washington, DC. (Dr. Noorali Bharwani)
Joggers near the Washington Monument, an obelisk at the National Mall in Washington, DC. (Dr. Noorali Bharwani)

After the age of 40, testosterone levels in men go down by 1% each year. Testosterone boosts mood, libido and muscle mass. It’s a $2 billion industry in the US, with millions of men buying testosterone gel, pills or getting injections.

Clinically, there is only one indication for prescribing testosterone. A man suffering from hypogonadism. Examples of this include failure of the testicles to produce testosterone because of genetic problems, or damage to the testicles from chemotherapy or infection.

Hypogonadism is a medical term for a defect of the reproductive system resulting in loss of function of the gonads. In men, it is the testes. The testicles have two functions: to produce hormones (testosterone) and to produce sperm.

Many men have been prescribed testosterone to boost sexual performance. A blood test will tell when testosterone is low. But doctors do not know what is a normal level for that individual or when the individual is getting too much testosterone.

The concern is that high testosterone level can cause heart attacks. Recently, the Food and Drug Administration (FDA) in the US has stepped up warnings for testosterone and other steroid drug prescribers and users. Testosterone is approved to treat men with medically diagnosed low levels of testosterone. The FDA does not approve the use of testosterone to treat the effects of aging.

The FDA says, “Not only can the drugs cause heart attacks, personality changes and infertility, but people can easily abuse them.”

There is a long list of reported serious adverse side effects including heart attack, heart failure, stroke, depression, hostility, aggression, liver toxicity, kidney failure, baldness and male infertility from shrinking testicles.

Individuals abusing testosterone have also reported withdrawal symptoms, such as depression, fatigue, irritability, loss of appetite, decreased libido and insomnia. It can also raise the risk of blood clots.

An article “Predicting low testosterone in aging men: a systematic review,” by Adam C. Millar and colleagues published in the Canadian Medical Association Journal (CMAJ June 20, 2016) says in men over 40, clinical signs and symptoms thought to be associated with low testosterone correlate poorly with testosterone levels.

Miller and his colleagues conducted a systematic review to estimate the accuracy of clinical symptoms and signs for predicting low testosterone among aging men. They found among 6053 articles identified, 40 met the inclusion criteria. The prevalence of low testosterone ranged between two per cent and 77 per cent. Threshold testosterone levels used for reference standards also varied substantially.

Authors of the CMAJ article found weak correlation between signs, symptoms and testosterone levels.

CMAJ editor’s comment: Until we know more about hypogonadism in older men, it’s prudent to be cautious in making the diagnosis and initiating treatment in this group.

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Treating Men with Testosterone Deficiency can be Challenging

Statue of Abraham Lincoln at the Lincoln Memorial in Washington, D.C. (Dr. Noorali Bharwani)
Statue of Abraham Lincoln at the Lincoln Memorial in Washington, D.C. (Dr. Noorali Bharwani)

Testicles produce a hormone called testosterone that plays an important role in the masculine growth and development during puberty. Testosterone also plays an important role in the production of sperms. Poor testicular function results in erectile dysfunction (impotence). There is a failure to get and maintain an erection firm enough for sex.

Testosterone deficiency syndrome (i.e. poor testicular function) affects approximately 40 per cent of men aged 45 or older, although less than five per cent of these men are actually diagnosed and treated for the condition. It may affect multiple organ systems and can result in substantial health consequences for men.

Despite some controversy, testosterone therapy has been established as a safe and effective principal treatment for poor testicular function for nearly 70 years. But there is no consensus among experts on how and when to treat men with this condition.

A recent article in the Canadian Medical Association Journal (CMAJ December 8, 2015) welcomes the new Canadian guideline from the Canadian Men’s Health Foundation. It is hoped that the new guideline will clarify the management of this condition in the light of the huge volume of research on this topic over the last five years.

In the past there have been multiple guidelines from different groups like European Association of Urology, the International Society for Sexual Medicine, the International Society for the Study of the Aging Male (2008), and the Endocrine Society guidelines of 2010.

One cannot treat a condition if it is difficult to make a diagnosis. The diagnosis of testosterone deficiency syndrome is not straightforward, says the CMAJ article. The reasons are several. There are limitations to testosterone measurement and there is lack of a valid symptom score. This makes it difficult for the primary care physicians to make a diagnosis and start treatment. Especially when the experts cannot agree on values (normal vs. abnormal blood levels of testosterone).

The new guidelines do not define normal/abnormal blood levels for making a diagnosis of testosterone deficiency syndrome. Instead, the authors put weight on a combination of factors – clinical history, physical examination and response to therapy – in making the diagnosis, in addition to measuring testosterone level.

The European Association of Urology and the International Society for Sexual Medicine set parameters that men with a total testosterone level of less than 8 nmol/L will usually benefit from treatment. A trial of therapy may be indicated for those with levels between eight and 12 nmol/L in the presence of substantial symptoms.

There is no consensus on how long the initial trial of testosterone should last. The Canadian guideline advises a three-month trial of treatment. Some experts disagree with that. They suggest the trial should last six-months to 12-months.

Some other points of interest:

  • More than three-quarters of men with type 2 diabetes have erectile dysfunction, and about 90 per cent have positive symptom scores for testosterone deficiency syndrome.
  • Injection of testosterone, especially long-acting formulations, has higher efficacy rates and safety benefits than topical treatment. Other options are gels, patches or oral pills.
  • Opinion varies on monitoring patients taking testosterone therapy e.g. checking effects of testosterone on prostate (PSA).

It is important to remember that many important clinical issues remain unresolved. This article is just a summary of important points. The reader is advised to consult with his physician for more information.

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New Guidelines for Use of Testestorone in Male Menopause

Do men undergo menopause? If yes, then how do we diagnose it and treat it?

The medical term for male menopause is andropause. “Andro” stands for androgen – a male sex hormone, such as testosterone or androsterone, which controls the development and maintenance of masculine characteristics. Andropause is also known as ADAM (androgen decline in the aging male).

Amongst physicians, some believe in male menopause and others do not. There is not a consensus case definition for androgen deficiency. The main reason is that the clinical manifestations of testosterone deficiency are usually subtle and variable. This results in poor understanding of the condition.

In order to provide an evidence-based foundation for diagnosis and management of andropause, the Endocrine Society recently published clinical practice guideline (J. Clin. Endo. Metab. 2010; 95:2536-59) to help physicians treat this poorly understood condition.

The full title of the document is, “Testosterone Therapy in Men With Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline.”

At what age does testosterone deficiency in men start?

The precise age at which testosterone levels start to decrease is not known. Testosterone levels decline by one to two per cent per year in older men, and the circadian (biological rhythm) variability of levels present in younger men is also commonly lost with aging, says the guideline. Hence, the symptoms of testosterone deficiency in men vary with the age of onset and degree of testosterone deficiency.

Aside from the normal aging decline in testosterone production by the testicles, there are many other reasons why testicular function may fail. Such as: testicular injury, infection, tumours, surgery and effect of other hormonal problems.

What kind of symptoms testosterone deficiency produces?

According to the guideline, the signs and symptoms most consistent with testosterone deficiency include decreased libido, erectile dysfunction, gynecomastia (enlargement of male breast), loss of body hair, hot flushes/sweats, bone loss and/or low-impact fractures, absence of sperms in the semen/infertility, and incomplete sexual development.

A variety of less-specific symptoms also may be attributable to testosterone deficiency: decreased energy or mood, sleep disturbance, poor concentration, modest anaemia and increased body fat with decreased muscle bulk/mass, says the guideline.

How to make a diagnosis?

Besides evaluating the clinical symptoms, a morning total testosterone level is the recommended initial test for androgen deficiency. If low, then this should be repeated to confirm the results. Some patients who suffer from chronic illnesses might require measurement of free testosterone levels.

Testosterone level is highest in early morning and can decrease by 35 percent in the mid-afternoon and evening. Early morning testosterone level less that 7 nmol/l indicates that a man has poor testicular function. This will warrant further investigation to find the reason for low level. Is it a primary testicular problem or secondary to other medical conditions?

The guideline is very specific in saying that testosterone deficiency should not be diagnosed without the presence of both symptoms and low testosterone levels.

Does testosterone therapy work?

The guideline says that the randomized trials of testosterone replacement in men with testosterone deficiency have shown consistent improvement in bone density, lean body mass with concomitant reduction in fat mass and sense of physical well-being.

The trials were less consistent in effects on muscle strength, libido, erectile function, quality of life, depression, cognition and muscle strength. Testosterone replacement has not been demonstrated to reduce fractures. Many of the trials are limited by small sample size and short follow-up.

Testosterone treatment is not recommended in men with breast or prostate cancer, elevated PSA, and/or unevaluated prostate abnormality, those at high risk for prostate cancer, those with severe lower urinary tract symptoms or in men with hematocrit greater than 50 per cent, untreated sleep apnea or poorly controlled heart failure. Men treated with testosterone replacement should be evaluated on regular basis.

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Male Menopause is Treatable

Yes, males do go through menopausal changes. As the joke goes, male menopause is a lot more fun than female menopause. With female menopause you gain weight and get hot flashes. With male menopause you get to buy a sports car, date young girls and drive motorcycles.

The correct name for male menopause is “andropause”. “Andro” stands for androgen – a male sex hormone, such as testosterone, that controls the development and maintenance of masculine characteristics. The onset of andropause is unpredictable. Its clinical manifestations are subtle and variable.

The symptoms of andropause include fatigue, depression, hot flushes, sweats, decreased libido, erectile dysfunction, changes in cognition (like poor concentration and memory) and mood. Since these symptoms are more subjective than objective, some experts have trouble accepting andropause as a clinical condition.

Physical examination of an aging male patient with andropause may be quite normal. There may be presence of gynaecomastia (enlargement of male breast) and/or soft small testicles. Low testosterone level does not produce any specific organ changes.

Diagnosis of andropause is made by symptoms, physical signs and early morning non-fasting specimen of blood for testosterone level. Testosterone level is highest in early morning and can decrease by 35 percent in the mid-afternoon and evening.

Early morning testosterone level less that 7 nmol/l indicates that a man has poor testicular function. Testosterone level found to be critical for sexual function in men is around 10.4 nmol/l. There can be some variation between individuals.

Normally men experience a continuous slow (an average of one to two percent a year) decline in serum testosterone level after about age 30 years. This is due to decrease in testosterone production. There are many other reasons why testicular function may fail – injury, infection, tumours, surgery and effect of other hormonal problems.

The goals of treatment for poor testicular function are to improve erectile function, restore libido, and improve psychological well-being and mood. It is important to remember that in men over 50, cause for erectile dysfunction may be other than low testosterone level. So testosterone replacement therapy will improve libido and psychological well-being in this age group but may occasionally improve erectile dysfunction. Testosterone replacement therapy improves bone mass, coronary artery disease, reduces total cholesterol and LDL (bad cholesterol) levels.

Testosterone should not be given to individuals with prostate or breast cancer. Sleep apnea has been shown to contribute to low serum testosterone levels and testosterone therapy has been reported to make sleep apnea worse. Testosterone therapy may make blood thick (polycythemia), promote benign and malignant changes in the prostate, and can cause tenderness and enlargement of breasts.

Testosterone is available for clinical use in many forms: injectable, oral pill, skin patch, gel and implantable formulations. Each one has advantages and disadvantages. Your physician will advice you the best formulation for you. The physician should monitor the treatment to check for any side-effects and for any long term complications like prostate cancer.

So there is hope for aging men. Besides sports cars and motor bikes, there is Viagra and testosterone. You will be laughing and driving your motor bike all the way to a nursing home when you are 90 or 100. But talk to your doctor first before you put your life’s savings in a sports car.

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